The present invention relates to a new intermediate involved in the synthesis of clavulanic acid and an enzyme useful in the synthesis of clavulanic acid from intermediates involved in its biosynthesis. The present invention also relates to processes for preparation of the enzyme and intermediate. The present invention further relates to DNA molecules carrying a gene coding for an enzyme involved in clavulanic acid biosynthesis.
The biosynthetic route to the important product clavulanic acid, a key ingredient of the antibiotic AUGMENTIN (Trade Mark of SmithKline Beecham plc) has been the subject of considerable study with a view to increasing the yield (titre) of clavulanic acid in fermentation processes. Clavulanic acid has been shown to be derived biosynthetically from clavaminic acid. 
It has been reported (J. Chem. Soc., Chem. Commun. 1987, 1737 and 1990, 617) that clavaminic acid is formed by the action of an enzyme on a precursor known as proclavaminic acid (see also EP-A-0213914). Earlier steps in the biosynthetic pathway have been more difficult to elucidate.
We have now established that the final reaction in the biosynthesis of clavulanic acid involves the reduction of a side chain aldehyde to the hydroxyl group, using NADPH as the hydrogen donor.
The involvement of an aldehyde in the biosynthetic pathway has been suggested previously (Townsend et al. 1988, J Chem Soc Chem Commun, 18, 1234-36; Iwata-Reuyl, D and Townsend, C. A. 1992, J AM Chem Soc 114, 2762-4), however the present work represents the first isolation and proof of the existence of such a compound.